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Publication : Stimulation of histamine H4 receptor participates in cold-induced browning of subcutaneous white adipose tissue.

First Author  Zhao YX Year  2019
Journal  Am J Physiol Endocrinol Metab Volume  317
Issue  6 Pages  E1158-E1171
PubMed ID  31550180 Mgi Jnum  J:282988
Mgi Id  MGI:6384082 Doi  10.1152/ajpendo.00131.2019
Citation  Zhao YX, et al. (2019) Stimulation of histamine H4 receptor participates in cold-induced browning of subcutaneous white adipose tissue. Am J Physiol Endocrinol Metab 317(6):E1158-E1171
abstractText  Although many studies have shown that histamine and its signaling regulate energy homeostasis through the central nervous system, their roles in adipose tissues remain poorly understood. Here, we identified that the histamine H4 receptor (HrH4) was highly expressed in adipocytes at a level higher than that of the other three receptors (i.e., HrH1, HrH2, and HrH3). The HrH4 expression in adipocytes responded to cold through thermogenesis and lipolysis, supported by results from both mouse and cell models. When HrH4 expression was knocked down in the subcutaneous white adipose tissue (scWAT), browning and lipolysis effects triggered by cold were ablated, and the oxygen consumption was also lowered both at the normal and cold conditions. Moreover, mice exhibited browned scWAT, accelerated metabolic rates, and tolerance to hypothermia when 4-methylhistamine (4MH), a selective HrH4 agonist, was adjacently injected to the scWAT. Consistent with these findings, 4MH also triggered the browning and lipolytic effects in cultured C3H10T1/2 adipocytes. Mechanically, we demonstrated that p38/MAPK and ERK/MAPK pathways were involved in these processes. In conclusion, our findings have uncovered an effective role of HrH4 in adipose tissue browning.
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